Premium
The Amyloid Fibril‐Forming Properties of the Amphibian Antimicrobial Peptide Uperin 3.5
Author(s) -
Calabrese Antonio N.,
Liu Yanqin,
Wang Tianfang,
Musgrave Ian F.,
Pukala Tara L.,
Tabor Rico F.,
Martin Lisandra L.,
Carver John A.,
Bowie John H.
Publication year - 2016
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201500518
Subject(s) - fibril , antimicrobial peptides , chemistry , peptide , amphibian , biophysics , random coil , membrane , innate immune system , amyloid (mycology) , biochemistry , protein secondary structure , biology , ecology , inorganic chemistry , receptor
The amphibian skin is a vast resource for bioactive peptides, which form the basis of the animals' innate immune system. Key components of the secretions of the cutaneous glands are antimicrobial peptides (AMPs), which exert their cytotoxic effects often as a result of membrane disruption. It is becoming increasingly evident that there is a link between the mechanism of action of AMPs and amyloidogenic peptides and proteins. In this work, we demonstrate that the broad‐spectrum amphibian AMP uperin 3.5, which has a random‐coil structure in solution but adopts an α‐helical structure in membrane‐like environments, forms amyloid fibrils rapidly in solution at neutral pH. These fibrils are cytotoxic to model neuronal cells in a similar fashion to those formed by the proteins implicated in neurodegenerative diseases. The addition of small quantities of 2,2,2‐trifluoroethanol accelerates fibril formation by uperin 3.5, and is correlated with a structural stabilisation induced by this co‐solvent. Uperin 3.5 fibril formation and the associated cellular toxicity are inhibited by the polyphenol (−)‐epigallocatechin‐3‐gallate (EGCG). Furthermore, EGCG rapidly dissociates fully formed uperin 3.5 fibrils. Ion mobility–mass spectrometry reveals that uperin 3.5 adopts various oligomeric states in solution. Combined, these observations imply that the mechanism of membrane permeability by uperin 3.5 is related to its fibril‐forming properties.